Summary Restoring vision to the blind has been an age-old dream, but it took an avalanche of biomedical research and development over the last few decades to begin turning this dream into reality. In recent years the potential of saving and restoring sight has been demonstrated in vitro, in animal models, and in some cases even in human patients. With the advent of early clinical trials for these therapies, often primarily aimed at safety and enrolling patients with profound vision loss, there is a growing need for vision assessments that not only can measure rudimentary vision, but reliably demonstrate small changes. Ideally these measures should also demonstrate efficacy in real-world situations, and include the use of vision for tasks such as eye-hand coordination, orientation, and mobility. In our laboratory we have demonstrated that the properties of rudimentary ?native? vision can be assessed with a visual functioning questionnaire specifically designed for ultra-low vision, the ULV-VFQ, and with a set of standardized visual activities of daily living, the ULV-ADL. Moreover, we demonstrated that the performance of users of the Argus II retinal prosthesis system and the BrainPort vision substitution device is very similar to that of individuals with native ULV. This application lays out a program to validate the previously completed assessments in a larger ULV population (Aim 1), to develop a range of additional assessments (Aim 2), to translate a subset of the visual activities used in these assessments to real-world situations and minimize redundancies (Aim 3), and to assess the similarity in performance between individuals with native ULV and recipients of the Argus II, BrainPort, and other sight-restoring treatments (Aim 4). The new assessments under Aim 2 will cover instrumental activities of daily living (IADL) and orientation & mobility (O&M), and all assessments will cover both static and dynamic scenarios. Our long-term collaborator Dr. Duane Geruschat will act as a consultant in the design and evaluation of these assess.ements. Human subjects testing will be carried out at the Johns Hopkins Wilmer Eye Institute and the Chicago Lighthouse, which not only counts a substantial ULV population among its employees and clients, but also a number of BrainPort users. Investigators at both sites have extensive research experience with this population. O&M scenarios under Aim 2 will be realized in virtual reality with the assistance of our partners at Balti Virtual. The resulting assessments promise to not only have a major impact on future clinical trials of sight-restoring therapies, but also lay the foundation to rehabilitation approaches for recipients of such therapies.